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To describe the sources of uncertainty in prognosticating devastating brain injury, the role of the intensivist in prognostication, and ethical considerations in prognosticating devastating brain injury in the ICU.A PubMed literature review was performed.Articles relevant to prognosis in intracerebral hemorrhage, acute ischemic stroke, traumatic brain injury, subarachnoid hemorrhage, and postcardiac arrest anoxic encephalopathy were selected.Data regarding definition and prognosis of devastating brain injury were extracted. Themes related to how clinicians perform prognostication and their accuracy were reviewed and extracted.Although there are differences in pathophysiology and therefore prognosis in the various etiologies of devastating brain injury, some common themes emerge. Physicians tend to have fairly good prognostic accuracy, especially in severe cases with poor prognosis. Full supportive care is recommended for at least 72 hours from initial presentation to maximize the potential for recovery and minimize secondary injury. However, physician approaches to the timing of and recommendations for withdrawal of life-sustaining therapy have a significant impact on mortality from devastating brain injury.Intensivists should consider the modern literature describing prognosis for devastating brain injury and provide appropriate time for patient recovery and for discussions with the patient’s surrogates. Surrogates wish to have a prognosis enumerated even when uncertainty exists. These discussions must be handled with care and include admission of uncertainty when it exists. Respect for patient autonomy remains paramount, although physicians are not required to provide inappropriate medical therapies.